Fetal programming of human energy homeostasis brain networks: Issues and considerations

In this paper, we present a transdisciplinary framework and testable hypotheses regarding the process of fetal programming of energy homeostasis brain circuitry. Our model proposes that key aspects of energy homeostasis brain circuitry already are functional by the time of birth (with substantial interindividual variation); that this phenotypic variation at birth is an important determinant of subsequent susceptibility for energy imbalance and childhood obesity risk; and that this brain circuitry exhibits developmental plasticity, in that it is influenced by conditions during intrauterine life, particularly maternal-placental-fetal endocrine, immune/inflammatory, and metabolic processes and their upstream determinants. We review evidence that supports the scientific premise for each element of this formulation, identify future research directions, particularly recent advances that may facilitate a better quantification of the ontogeny of energy homeostasis brain networks, highlight animal and in vitro-based approaches that may better address the determinants of interindividual variation in energy homeostasis brain networks, and discuss the implications of this formulation for the development of strategies targeted towards the primary prevention of childhood obesity.